NEUROPSYCHIATRIC COMPLICATIONS OF

ALCOHOL DEPENDENCE SYNDROME

PRESENTER- Dr. PAVITHRA

C/P- Dr. SIDDHARTH SHETTY

INTRODUCTION

Alcohol is remarkable both for its long history & ubiquity of use & for diverse range of neuropsychiatric disorders it can produce.

Half of drinkers experience temporary alcohol related problems like impaired memory & blackouts etc..

Common during intoxication & withdrawal.

Clinician has to distinguish between temporary alcohol-related psychopathology which is likely to disappear after abstinence and independent psychiatric syndromes that may require long-term support and medications.

80% of ADS patients develop temporary symptoms out of which around 40% persist enough to meet the criteria for major psychiatric disorders.

Neuropsychiatric complications can be classified as:

1. Direct effects- alcohol intoxication, aggression, blackouts,

2. Disorders due to withdrawal- tremors, seizures, hallucinoses, delirium tremens.

3. Associated nutritional deficiencies- Wernicke’s encephalopathy, Korsakoff’s syndrome, Peripheral neuropathy, Cerebellar degeneration.

4. Alcohol induced conditions- dementia, mood disorder, anxiety disorder, psychotic disorder.

5. Resultant end stage liver disorder or bone marrow suppression ensuing their own neuropsychiatric complications- hepato-cerebral degeneration.

ALCOHOL INTOXICATION

Effects of alcohol are sensitive to dose (blood level alcohol), timing ( rising/ declining), & social context.

CNS depressant- target on GABA A receptor augmentation of GABA neurotransmission.

Associated with early net effects on opioidergic & dopaminergic neurotransmission in ventral striatal reward pathways.

Early effects produce stimulation, subjective exhilaration, excitement & loquacity.

Personality factors, environmental & cultural influences shape outward evidence of intoxication.

At higher doses there is net depressant effects on wide spread cortical networks leading to:

Level

20–30 mg/dL

(.2–.3g/dL)

30–80 mg/dL

80–200 mg/dL

200–300 mg/dL

>300

Likely Impairment mg/dL

Slowed motor performance and decreased thinking ability

Increases in motor and cognitive problems

Increases in incoordination and judgment errors. Mood lability. Deterioration in cognition

Nystagmus, marked slurring of speech, and alcoholic blackouts

Impaired vital signs and possible death

Mellanby effect- symptoms depend on rate of rise of blood concentrations to given level & length of time alcohol is present in body.

Quick rise will produce effects at a lower level of blood alcohol than gradual rise.

For a given rate of rise the effects will be less marked if alcohol has been present at a constant level sometime before

AGRESSION

Mechanism:Psychostimulant effect

Diminished anxiety & pain perception

Impaired inhibition.

Severe form- pathological intoxication,

alcohol idiosyncratic intoxication, acute

alcoholic paranoid state, manie a potu

Presents as an outburst of uncontrollable rage & excitement leading to destructive actions against other persons & property.

Behavior is described as out of character for the individual concerned, duration is short, & there is subsequently amnesia for entire episode.

Coid- found nothing to support the notion.

ALCOHOLIC BLACKOUT’S

characterized by memory impairment (anterograde amnesia) for the period when a person was drinking heavily but remained awake.

Is the result of the ability of high doses of any brain depressant (e.g., alcohol or benzodiazepines) to interfere with the acquisition and solidification of memory.

40 percent of drinkers have at some time had a blackout

The memories might return with passage of time & some times recall was facilitated by further drinking.

Occurrence is directly related to

severity & duration of drinking.

Pathogenesis- uncertain.

State dependent training-learning transfer was proved to be better when the subject was intoxicated in both the first & 2nd tests sessions than when intoxicated in the first but sober in the 2nd.(Goodwin et al)

SLEEP IMPAIRMENT

Alcohol helps a person fall asleep more quickly, but if the intake in an evening is > 1 or 2drinks, the subsequent sleep pattern is likely to be impaired.

Alcohol Suppresses REM sleep,

inhibits stage 4 sleep late in the night,

subsequently associated with frequent alternations between sleep stages (sleep fragmentation) & more intense & disturbing dreams late in the night as blood alcohol level falls.

WITHDRAWAL SYNDROMES

consists of two components.Physical signs such as tremor which are determined by the degree of physical dependence developed during the most recent drinking bout.

Seizures hallucinations & delirium that reflect long term CNS dysfunction accruing over many years of repeated intoxication & withdrawal

Tremors, nausea & transient hallucination in clear consciousness- 3-12 hrs

Seizures- 12- 48 hrs

Delirium tremens- 3- 4 days

Temporary alleviation on

taking alcohol.

TREMORS

Commonest, associated with general weakness, nausea & irritability.

Mild forms- occur after a single night’s abstinence & after a period of drinking for only several days.

Severe forms- 12- 24 hrs after stopping, only after continuous weeks of drinking.

Subsides over several hrs or

days but after severe attacks

may take 1- 2 weeks

HALLUCINOSIS

¼ of tremulous patients have disordered sense perception- transitory misperceptions of familiar objects to illusions & hallucinations

Benign lasting less than 24 hrs- few days.

Hallucinations- visual/ auditory, fleeting in clear consciousness.

Auditory- simple, tinnitus common

Visual- blurring, flashes of light, moving animals usually distorted

Cause- withdrawal of alcohol, ? Thiamine deficiency.

Alcoholic hallucinosis- rare, verbal auditory hallucinations occur alone.

Buzzing, roaring, ringing of bells, threatening voices, derogatory remarks, command hallucinations, third PAH.

Secondary delusional interpretations follow

Similar to schizophrenia- no thought disorder, delusions follow only hallucinatory experience, no incongruity of affect & insight is regained.

90% transient & disappears within a week, few persists for months – years.

Factors which determine prolongations of hallucinations or transit to schiz like illness remain unknown.

Repeated attacks may make patient ultimately more vulnerable to the type of attack leads on to schizophrenic deterioration.

WITHDRAWAL SEIZURE

Consumption of alcohol can precipitate seizures in person with seizure disorder.

Withdrawal seizures or rum fits occurs in person without predisposition of seizure

Occur after heavy consumption, usually within 12- 24 hrs of termination of long continued bout

Occasionally occur while consumption continues due to transient fall in blood alcohol levels

Usually GTCS bouts of 2- 6 at a time, rare- status epilepticus

30 % fits DT. 30% DT & 10% AH seizures

EEG- abnormal during episode but reverts back to normal

DELIRIUM TREMENS

Most serious with mortality of upto 5%

Fully developed consists of vivid hallucinations, delusions, profound confusion, tremor, agitation, sleeplessness & autonomic overactivity..

Uncommon- < 5% of withdrawals.

McNichol (1970) recognised 3 grades in development of complete syndrome.

Mental sluggishness with tremor & evidence of residual intoxication.

Emotional lability, agitation, fearfulness, increased PMA, autonomic disturbance, nightmares,& disorientation.

Onset of definitive DT.

Autonomic hyperactivity- diagnostic importance.

C/F- sudden onsetUsually at night,

Restlessness, fear, insomnia

Startles with least sound

Vivid nightmares

Transient illusions & hallucination

(visual, auditory, tactile)

Insight retained

Fluctuating levels of consciousness

tremulous

Severe cases- ataxia, dehydration

Autonomic disturbance- perspiration, flushing, pallor, dilated pupils, weak rapid pulse & mild pyrexia

Epileptic seizures- 1/4th

Slurred speech with paraphasias, incoherent, fragmented

EEG- fast activity

Outcome- short lived, less than 3 days

COGNITIVE IMPAIRMENT & CEREBRAL ATROPHY

Long continued abuse of alcohol lead to severe cognitive impairment- contributory cause

10% of patients suffer from mild- severe forms.

Deficits in memory, visuospatial competence, abstracting ability, & complex reasoning.

Psychological assessments during first few weeks of abstinence show substantial recovery of intellectual & memory functions for a period of several months.

By 1 yr psychological deficits persists in:Tests of psychomotor speed,

perceptual- motor functioning

visuospatial competence

Abstracting ability & reasoning

memory

New learning capacity impaired

Impaired capacity for complex figure ground analysis.

Deficits in frontal lobe functions- personality change, circumstantiality, plausibility, weakness of volition

Vicious cycle with worsening of cognitive status contributing to potentiation of addiction.

Women more vulnerable. With visuospatial function & verbal & non verbal memory impairment.

Abstainers improve more than alcoholics who initially abstain but return to drinking.

Older age- brain damage+ alcohol+ other pathologies ( ageing, trauma, vascular changes, hepatic dysfunction) serious & irreversible changes.

Neuropathology: Cerebral atrophy- mild- moderate

White matter in cerebrum is reduced & ventricles enlarged by 1/3rd.

Thickness of corpus callosum reduced by 20%.

Micro- arachnoidal thickening & cell degeneration & loss in smaller of superficial & intermediate laminae

Marked alterations in dendritic morphology in hippocampal pyramidal neurons, dentate granular layers & cerebellar vermis cell degeneration & loss.

22% reduction in number of neurons in superior frontal cortex with reduction in size of neurons in motor & cingulate cortices

Disintegration of nerve fibres.

More lesions in base of brain & cerebellum- wernicke

Direct toxic affects + thiamine def disruption of monoaminergic & cholinergic inputs to cortex cognitive deficits.

Quantitative study of extent of dendritic arborisation in layer III pyramidal neurons from frontal & motor cortex- significant reductions in mean dendritic length, number of branches, & mean width of basal dendritic fields.

Abstinence allows regrowth of dendritic branching & return to normal thickness of strata plasticity inherent in adult brain with regard to dendritic growth & sprouting.

Neuroimaging: 50- 70% of severe chronic alcoholics show cortical

shrinkage or ventricular dilations or both.

Changes found in young alcoholics within the first decade of alcohol abuse, more marked in older age groups.

Planimetric measures of lateral ventricular size show 50% enlargement

Atrophy of cerebellar vermis & frontal lobes- high proportion.

Females more vulnerable.

1/3rd subjects show normal scans.

MRI: ventricular enlargement & increase in CSF over cortical surface.

Significant reductions in grey matter in medial temporal, superior frontal & parietal regions

Subcortical grey matter was reduced- caudate nucleus & diencephalon

Changes in cerebellar volume

White matter degradation on diffuse tensor imaging.

Clinical association:Duration & severity of alcohol abuse- little relation severity of cerebral changes

Indirect evidence that episodic drinking may be less harmful.

Duration of abstinence- increasing length of abstinence prior to scanning, changes become less pronounced.

Some degree of persistent ventricular enlargement remains.

Significant decrease in both ventricular size & suarachnoid spaces during early weeks of abstinence- ? Dehydration & rehydration of brain, increased protein synthesis, or incresed dendritic growth.

WERNICKE’S ENCEPHALOPATHY

Neuropsychiatric reaction to severe thiamine deficiency.

Disorder of acute onset characterised by nystagmus, abducens & conjugate gaze palsies, ataxia of gait & global confusional state.

Wernicke first described it in 1881 as polioencephalitis haemorrhagica superior.

Alexander in 1940 demonstrate lesions

in the brains of thiamine deficient

pigeons

Alcohol leads to thiamine deficiency:Replacement of vitamin containing foods by alcohol

Impaired absorption of thiamine from gut.

Impairment of storage by liver

Decreased phosporylation to thiamine pyrophosphate.

Excessive requirements for metabolism of alcohol

In 50% of patients suffering from WE evidence of alcohol is reported.

Place to place prevalence varies- beverage consumed, its thiamine content, patterns of drinking & patterns of dietary neglect.

Thiamine in form of thiamine pyrophosphate is important for:

Transketolase- essential for maintenance & synthesis of myelin.

Pyruvate dehydrogenase & alpha ketoglutarate dehydrogenase- role in brain glucose metabolism & energy production.

Personal susceptibility in form of inborn abnormality by way of reduced affinity between TPP & enzymes.

Transketolase exists in a number of isoenzyme variants.

WERNICKE’S ENCEPHALOPATHY:

Encephalopathy appeared when acute & severe thiamine depletion was superimposed on partial deficiency whereas other forms (cardiac & neuritic) resulted from less severe&& more prolonged lack.

CLINICAL FEATURES:

Onset- abruptly.

Commonest presentations- mental confusion or staggering gait.

Triad- global confusion, ophtalmoplegia, ataxia

Harper et al found classic triad in 16%, 28% with 2 signs, 37% with one & 19% with no signs.

Other features- prodromal anorexia, nausea, vomiting, marked memory disturbance, lethargy, hypotension, hypothermia, stupor coma.

Age- throughout adult life.

Males twice affected.

Pattern- steady drinking extending over months or years coupled with inadequate food intake.

O/E Victor et al found: Ocular abnormalities- 96%

Nystagmus, sixth nerve palsies producing lateral rectus weakness, conjugate gaze paralysis.

Pupils- sluggish. Signs evanescent, resolves easily with treatment.

Ataxia- 87% Inability to stand, differences in heel toe walking. Intention tremor in legs/ arms- rare.

Peripheral neuropathy- 82% confined to legs Subjective complains of weakness, paraesthesia & pain

Serious malnutrition- 84% Redness or papillary atrophy of tongue, cheilosis, angular

stomatitis, telangiectases, dryness & discolaration of skin.

Evidence of liver disorder in 2/3rd. Abstinence syndrome – 13%

Epileptic fits, hallucinoses, delirium tremens

Mental abnormalities- 90% Commonest- global confusion with disorientation, apathy,

derangement of memory. Drowsy, marked indifference & inattention to their

surrounding.

Impairment of consciousness rarely profound or persistent. Spontaneous activity & speech minimal- irrational or

inconsistent. grasp, awareness, responsiveness impaired Misidentifications, physical & mental fatigability,

concentration difficulties Perceptual distortions,, vivid hallucinations, insomnia,

agitation, autonomic overactivity- evanescent & not severe. When confusion reduces- defect in memory with 14% of

typical Korsakoff memory defect. Confabulation common in early stages.

Subclinical forms common

Pathology:Symmetrical lesions found predominantly around wall of third ventricles, periaqueductal region, floor of fourth ventricle, thalamic nuclei ( paraventricular parts of medial dorsal nuclei, anteromedial nuclei & pulvinar). Mamillary bodies, terminal portions of fornices, brain stem, anterior lobe & superior vermis of cerebellum.

Convolutional atrophy- 27%

Micro- affects neural elements (neurons, axis cylinders, blood vessels & glia)

- myelinated fibers affect more

- astrocytic & histiocytic proliferation, proliferation of blood vessels, petechial heamorrhages ( terminal)

Ophthalmoplegia- lesion of 3 & 6 CN nuclei & adjacent tegmentum.

Nystagmus- vestibular nuclei

Ataxia- vestibular nuclei & anterior lobes & vermis of cerebellum.

Lesion in mamillary body, mamillo thalamic tract, anterior nuclei of thalamus critical for persistent & severe anterograde memory deficit ok Korsakoff syndrome.

Investigations:

EEGdiffuse slowing- 50%

prominent generalised asynchronous slow waves

bysynchronous slow waves

Decrease of alpha rhythm

CSF- mild elevation of protein

CT- symmetrical areas of decreased attenuation in region of thalamus.

MRI- atrophy of mamillary bodies, hyperintensities surrounding third ventricle & aqueduct, reductions in both white & grey matter cerebral blood flow.

COURSE & RESPONSE TO TREATMENT:

Sixth nerve palsies recovered – hrs to days

Horizontal nystagmus persist- 2/3rd

Ataxia improve within first week- month

1/4rd ataxia persists,1/2 left with permanent unsteadiness of some degree.

Polyneuropathy disappears slowly

Diminution or absence of tendon reflexes- permanent

Global confusion- recovers 2-3 weeks & disappears by 1-2 months.

84% develop- typical amnesic syndrome.

KORSAKOFF’S SYNDROME

Described by Korsakoff in 1887

Named as psychosis polyneuritica

Cause- ? Thiamine deficiency/ ? Direct effect of alcohol.

Link between WE & KS

Onset- delayed for weeks to months.

Continues for 2 yrs.

Clinical features: anterograde & retrograde (several years) amnesia,

Relative preservation of other cognitive functions

Subtle deficits in visuoperceptive & abstract ability

Confabulation in chronic stage.

Impaired executive functions & frontal lobe tests

Course-Complete recovery in ¼

Partial recovery in ½

Rest no improvement.

Neuroimaging:

CT-Wider third, lateral ventricle, sylvian fissures & interhemispheric fissures.

Atrophy in frontal sulcal & perisylvian areas

MRI-Greater grey matter losses in medial temporal & orbitofrontal cortex

Significant reduction in thalamic volumes

SPECT- impaired flow in frontal regions

PET- 20% reduction in glucose metabolism with hypometabolism in cortical areas, thalamus & BG

- hypometabolism in 3 areas- thalamic, venteromedial frontal, retrosplenial regions

EEG- mild- moderate generalised slowing

PERIPHERAL NEUROPATHY

Cause- thiamine deficiency with pyridoxine & pantothenic acid deficiency, neurotoxic effect of alcohol, toxins in beverages

C/F-Symptomless

Sensory disturbances- numbness, pins & needles, burning sensation in feet

Weakness progress to foot drop with wasting of leg muscles

Cutaneous sensory loss peripherally in hands & feet

Intense hyperasthesia on stoking skin

Tenderness in calf muscles

Odema of different parts

Dysphoric changes in skin & nails.

Loss of ankle reflexes

Isolated, associated with WE, KS, or DT

CEREBELLAR DEGENERATION

Uniform cerebellar degeneration with ataxia of stance & gait.

Arms little affects & nystagmus & dysarthria absent.

Slow progression- weeks – months, static for years

CT/ MRI- cerebellar cortical atrophy

PET- hypometabolism in superior cerebellar vermis

Pathological changes restricted to anterior & superior aspect of vermis & cerebellar hemispheres

Purkinje cell loss

AMBLYOPIA

Retrobulbar neuritis- complete blindness, rare

Progress over 1- 2 weeks

Dimness for central vision, red & green

Associated with peripheral neuropathy

Smoking associated

Deficiency of thiamine & vit B 12

Acute blindness- common in methyl alcohol poisoning due to direct toxic effects

MARCHIAFAVA- BIGNAMI DISEASE

Rare, formerly thought to be restricted to Italian males & vine consumption

C/F- ataxia, dysarthria, epilepsy & severe impairment of consciousness, slowly progressive forms with dementia, spastic paralysis of limbs.

Extensive demyelination affects corpus callosum, adjacent subcortical white matter, optic tracts & cerebellar peduncles

Mortality high, recovery late

CT/ MRI-lesions in corpus callosum

? Nutritional deficiency

CENTRAL PONTINE MYELINOLYSIS

Acute & fatal complication

C/F- obtundation, bulbar palsy, quadriplegia, loss of sensation in limbs & trunk

- vomiting, confusion, disordered eye movements, coma- common

- locked in syndrome- mutism & paralysis but relatively intact sensation & comprehension

Lesion lies in center of basal pontis & adjacent areas

MRI- focus of demyelination

Also seen in conditions causing hyponatraemia- severe burns, hyperemesis over rapid correction affecting pons osmotic demyelination syndrome

ALCOHOL INDUCED PSYCHIATRIC CONDITIONS

Present during intoxication or withdrawal states

Usually remit by 4 weeks & completely disappear by 6 months of abstinence

If persists >6 months consider independent disorderMOOD DISORDER

Depressive/ mania symptoms which meet criteria

80% report h/o intense depression, 30- 40% depressed > 2 weeks & only 10- 15% meet criteria for MDD= general population

Several weeks to 1 month patients presents with mood swings or intermittent symptoms of sadness- cyclothymia/ dysthmia

ANXIETY DISORDER

80% report panic attack, other symptoms like that of social phobia, agoraphobia

PSYCHOTIC DISODER

3% experience auditory hallucinations, or paranoid delusions

UNSPECIFIED

HEPATOCREBRAL DEGENERATION

Hepatic encephalopathy- altered sensorium, frontal release signs, ‘metabolic' flapping tremor, hyper-reflexia, extensor plantar responses, and occasional seizures.

some patients progress from stupor to coma and then death, others recover and suffer recurrent episodes.

brain shows enlargement and proliferation of protoplasmic astrocytes in the basal ganglia, thalamus, red nucleus, pons, and cerebellum, in the absence of neuronal loss or other glial changes.

Patients who do not recover fully after an episode of hepatic encephalopathy go on to develop a progressive syndrome of tremor, choreoathetosis, dysarthria, gait ataxia, and dementia.

Hepatocerebral degeneration may progress in a stepwise fashion,

APPROACH TO PATIENT

Detailed history from patient ( if possible), family members, regarding the symptoms, onset, variation, past history etc.(Rule out organic causes & independent psychiatric disorders.)

Detailed examination (MSE, GPE, Systems)

Investigations.Treatment

a timeline should be established noting:

(1) the approximate age of onset of alcohol problems severe and repetitive enough to justify a diagnosis of alcohol dependence

(2) periods of abstinence of several months or more, and

(3) the ages at which the patient met the criteria for the major psychiatric disorders, taking care to emphasize full-blown psychiatric clinical conditions, not isolated symptoms.

Other specific tests-Frontal lobe tests

Neuropsychological battery

Intelligence tests

INVESTIGATIONS • Hemogram• ABG• ECG• LFT,RFT, TFT• Electrolytes• Blood sugar• Urine drug screen/ blood alcohol concentrations• Blood ammonia levels• ECG, ECHO, CXR• Lumbar puncture & CSF analysis• CT/ MRI/ EEG/ SPECT/ PET

DIFFERENTIAL DIAGNOSIS

Mood disorder

Psychotic disorder

Dementia

Medical causes

Anxiety disorders

ADHD

Other substance disorders

COMORBIDITIES

Personality disorders

Mood/ psychotic disorders/ anxiety disorders/ anxiety disorders/ dementia

Other substance use disorders

TREATMENT

Intoxication- acute episode/ severely intoxicated observation in case of alcoholic coma

Aggression- sedation with antipsychotics/ benzodiazepines

Intravenous high potency vitamin B & C can reduce subjective effects of intoxication & improve performance- rarely needed

Alcoholic coma- managed in hospital, rule out head injury, hypoglycemia, & other complications of alcohol

Maintain airway, breathing & circulation

May require IV fluids, vasopressor drugs & steroids

Thiamine supplementation before glucose transfusion

IV fructose or peritoneal dialysis- rare

Withdrawal – minor- OP, long acting sedatives

Complications- admission, sedatives titrated according to symptoms

Delirium- adequate fluid replacement, & sedation

Other complications to be treated accordingly

Wernicke’s encephalopathy- acute medical emergency

IV/ IM infusion of large doses of thiamine ( 200- 300 mg) slowly over 10 mins twice daily for a period of minimum 5 days

Oral thiamine for several months

Refractory- hypomagnesaemia ruled out

Other complications- infections, dehydration, electrolyte imbalance, cardiac failure

Korsakoff’s syndrome- treatment disappointing. High dose thiamine replacement by parenteral followed by oral for many months

Paripheral neuropathy- vitamin supplementation- slow improvement

Alcohol induced psychotic disorder- no treatment required. Spontaneously remits on abstinence.

Role of psychiatrist is not only to manage the treatment of withdrawal symptoms of ADS & prevention of relapse but also to treat the associated complications, especially neuropsychiatric, as they cause severe impairment & socio- occupational dysfunction.

Goal should be aimed at a better symptom free life for the patient which not only improves the work performance but also may also act to prevent relapse

THANK

YOU